Leontino Battistin

Effects of Fluoxetine and Maprotiline on Functional Recovery in Poststroke Hemiplegic Patients Undergoing Rehabilitation Therapy

BACKGROUND AND PURPOSE In animals, drugs that increase brain amine concentrations influence the rate and degree of recovery from cortical lesions. It is therefore conceivable that antidepressants may influence outcome after ischemic brain injury in humans. We evaluated the effects of the norepinephrine reuptake blocker maprotiline and the serotonin reuptake blocker fluoxetine on the motor/functional capacities of poststroke patients undergoing physical therapy. METHODS Fifty-two severely disabled hemiplegic subjects were randomly assigned to three treatment groups; during 3 months of physical therapy, patients were treated with placebo, maprotiline (150 mg/d), or fluoxetine (20 mg/d). Before and at the end of the observation period, we assessed activities of daily living by the Barthel Index, degree of neurological deficit by a neurological scale for hemiplegic subjects, and depressive symptomatology by the Hamilton Depression Rating Scale. RESULTS The diverse treatments ameliorated walking and activities of daily living capacities to different extents. The greatest improvements were observed in the fluoxetine-treated group and the lowest in the maprotiline-treated group. Furthermore, fluoxetine yielded a significantly larger number of patients with good recovery compared with maprotiline or placebo. These effects of the drugs were not related to their efficacy in treating depressive symptoms. CONCLUSIONS Fluoxetine may facilitate or, alternatively, maprotiline may hinder recovery in poststroke patients undergoing rehabilitation. The effects of fluoxetine as an adjunct to physical therapy warrant further investigation, since treatment with fluoxetine may result in a better functional outcome from stroke than physical therapy alone.

Cortical atrophy is relevant in multiple sclerosis at clinical onset

IntroductionIncreasing evidence suggests relevant cortical gray matter pathology in patients with Multiple Sclerosis (MS), but how early this pathology begins; its impact on clinical disability and which cortical areas are primarily affected needs to be further elucidated.Methods115 consecutive patients (10 Clinically Isolated Syndrome (CIS), 32 possible MS (p-MS), 42 Relapsing Remitting MS (RR-MS), 31 Secondary Progressive MS (SP-MS)), and 40 age/gender-matched healthy volunteers (HV) underwent a neurological examination and a 1.5 T MRI. Global and regional Cortical Thickness (CTh) measurements, brain parenchyma fraction and T2 lesion load were analyzed.ResultsWe found a significant global cortical thinning in p-MS (2.22 ± 0.09 mm), RR-MS (2.16 ± 0.10 mm) and SP-MS (1.98 ± 0.11 mm) compared to CIS (2.51 ± 0.11 mm) and HV (2.48 ± 0.08 mm). The correlations between mean CTh and white matter (WM) lesion load was only moderate in MS (r = )0.393, p = 0.03) and absent in p-MS (r = )0.147, p = 0.422). Analysis of regional CTh revealed that the majority of cortical areas were involved not only in MS, but also in p-MS. The type of clinical picture at onset (in particular, pyramidal signs/symptoms and optic neuritis) correlated with atrophy in the corresponding cortical areas.DiscussionCortical thinning is a diffuse and early phenomenon in MS already detectable at clinical onset. It correlates with clinical disability and is partially independent from WM inflammatory pathology.

The effects of long-term rehabilitation therapy on poststroke hemiplegic patients.

Background and Purpose Rehabilitation therapy is believed to be useful during the first few months after stroke when recovery usually takes place. However, evidence exists that this may not be the rule for all stroke victims. Therefore, we investigated, in a selected group of poststroke patients, the profile of recovery in response to long-term rehabilitation therapy. Methods Fifty-one hemiplegic subjects unable to walk 3 months after stroke were enrolled in this study. Patients underwent consecutive periods of rehabilitation up to 2 years after the cerebrovascular accident. Autonomy in daily living activities and the degree of neurological compromission were periodically assessed with the Barthel Index and a neurological scale designed for hemiplegic subjects. The main features of the patients were also evaluated as a possible predictor of outcome Results In a consistent percentage of the patients, significant gains in gait and daily living abilities were observed during the first year and, in individual cases, during the second year after stroke. At the end of the study, 74% of the patients regained their capacity to walk without assistance, and up to 79% had a Barthel Index score above 70. Sphincter function, level of neurological impairments, and capacity in daily living activities are significantly related to the outcome of the patients as a whole but were not useful to anticipate the outcome of each patient. Conclusions These results suggest that disabled poststroke subjects may attain significative functional improvements in response to prolonged restorative therapy. However, the possibility of predicting the outcome of individual patients appears the major problem to solve in order to assign to long-term rehabilitation programs only patients whowill benefit from the therapy.

The uptake of various amino acids by the mouse brainin vivo

Abstract (1) An amino acid (glycine, tryptophan, aspartic acid, arginine, serine, threonine, isoleucine, methionine, valine, or histidine) was injected intraperitoneally into adult mice, and the uptake by the brain was measured at various time periods. There was no uptake of glycine and aspartate; that of the other amino acids was appreciable. The rate of increase was different for the various amino acids. (2) Uptake was concentration dependent; increasing plasma, valine, and histidine concentrations slightly resulted in brain levels above those of plasma. Although uptake increased with higher plasma levels, the decreasing brain-plasma concentration ratio at higher concentrations indicated a saturable component of uptake. (3) Uptake of one amino acid was inhibited by related compounds; the pattern of inhibition indicated the presence of transport classesin vivo similar to those found in brain slices. Interaction of amino acids was further shown by the effect of the administration of one amino acid on the cerebral levels of a number of other compounds. (4) The individual differences in the behavior of the various amino acids emphasizes the role that specific transport processes play in cerebral homeostasis and metabolism in the living brain.

Extensive cortical inflammation is associated with epilepsy in multiple sclerosis

IntroductionEpilepsy is three to six times more frequent in MS than in the general population. Previous studies based on conventional magnetic resonance (MR) imaging have suggested a possible correlation between cortical inflammatory pathology and epileptic seizures. However, pure intracortical lesions (ICLs) are unlikely to be demonstrated with conventional MR. We applied the double inversion recovery (DIR) sequence in relapsing remitting MS (RRMS) patients with or without epileptic seizures in order to clarify the relationship between ICLs and epilepsy in MS in vivo.MethodsTwenty RRMS patients who had epileptic seizures (RRMS/E) during the course of the disease were studied for the presence of ICLs. A group of 80 RRMS patients with no history of seizures and matched for gender, age, disease duration, Expanded Disability Status Scale (EDSS) grading, and T2 lesion volume (T2-WMLV) was selected as reference population. ICLs were detected by applying the DIR sequence.ResultsICLs were observed in 18/20 (90%) RRMS/E and in 39/80 (48%) RRMS (p = 0.001). RRMS/E showed five times more ICLs (7.2 ± 8.4) than RRMS (1.5 ± 2.4; p = 0.015). The total ICLs volume was 6 times larger in RRMS/E than in RRMS (1.2 ± 1.7cm3 versus 0.2 ± 0.2cm3, p = 0.016). No significant difference was observed between RRMS and RRMS/E with regard to the number and volume of juxtacortical lesions and T2-WMLV.DiscussionOur findings indicate that RRMS/E have more extensive cortical inflammation than RRMS patients with no history of epilepsy. Inflammatory ICLs may be responsible for epilepsy in MS.

A short review of cognitive and functional neuroimaging studies of cholinergic drugs: implications for therapeutic potentials

Summary. In the last 20 years a cholinergic dysfunction has been the major working hypothesis for the pharmachology of memory disorders. Cholinergic antagonists and lesions impair and different classes of cholinomimetics (i.e. acetylcholine precursors, cholinergic agonists and acetylcholinesterase inhibitors) enhance attention and memory in experiment animals, healthy human subjects and Alzheimer disease patients. In addition, acetylcholinesterase inhibitors improve different cognitive (i.e. visuospatial and verbal) functions in a variety of unrelated disorders such as dementia with Lewy bodies, Parkinson disease, multiple sclerosis, schizoaffective disorders, iatrogenic memory loss, traumatic brain injury, hyperactivity attention disorder and, as we recently reported, vascular dementia and mild cognitive impairment. In animals, different cholinomimetics dose-dependently increased regional cerebral metabolic rates for glucose (rCMRglc) and regional blood flow (rCBF), two indices of neuronal function, more markedly in subcortical regions (i.e. thalamus, hippocampus and visual system nuclei). In both healthy human subjects and Alzheimer disease patients acetylcholinesterase inhibitors increased rCMRglc and rCBF in subcortical and cortical brain regions at rest but attenuated rCBF increases during cognitive performances. Hence, acetylcholinesterase inhibitors may enhance cognition and rCMRglc by acting primarily on subcortical regions that are involved in attentional (i.e. thalamus) and memory (i.e. hippocampus) processes; such an effect probably is not specific for Alzheimer disease and can be beneficial in patients suffering from a wide array of neuropsychiatric disorders.

Neurological complications of celiac disease and autoimmune mechanisms: A prospective study

Humoral immune mechanisms may have a role in the neurological complications of celiac disease (CD). We assessed 71 CD patients for neurologic manifestations and presence of serum antibodies to neural antigens. Sixteen patients (22.5%) were found to have neurological deficits including headache, depression, entrapment syndromes, peripheral neuropathy, and epilepsy. Antibody reactivity to neural antigens was detected in 30/71 (42.2%) patients. There was no clear correlation between anti-neural reactivity and neurologic dysfunction. Follow-up of 62 patients did not reveal change in electrophysiology or antibodies, regardless of diet. However, in 2 patients with neuropathy, symptoms improved or worsened depending on the diet.

Neurolupus is associated with anti-ribosomal P protein antibodies: An inception cohort study

OBJECTIVE Serum IgG antibodies (Abs) to phosphorylated ribosomal (P ribosomal) proteins have been inconsistently associated with neuropsychiatric manifestations in systemic lupus erythematosus (SLE). Our aim was to assess whether serum IgG Abs to ribosomal P proteins are associated with neuropsychiatric SLE. PATIENTS AND METHODS We examined an inception cohort of 219 SLE patients. Neuropsychiatric SLE manifestations were characterized using the American College of Rheumatology (ACR) definition. Serum Abs to P ribosomal proteins were searched for by immunoblotting. In a subgroup of patients, Abs were investigated also in cerebrospinal fluid (CSF). RESULTS Abs to P ribosomal proteins were detected in 45 (21%) patients, 23 of whom (51%) with neuropsychiatric involvement. Abs to P ribosomal protein were present both in serum and CSF. Abs to P ribosomal proteins significantly correlated with psychosis (p=0.017), mononeuropathy multiplex (p=0.040), malar rash (p=0.004), serum anti-Sm Abs (p=0.042), and lupus anticoagulant (p=0.036). SLE onset age was significantly younger in patients with Abs to P ribosomal proteins. Logistic regression analysis confirmed the relationship between Abs to P ribosomal proteins and psychosis, malar rash, SLE onset age and lupus anticoagulant. CONCLUSIONS Abs to ribosomal P proteins are associated with psychosis and might be associated with peripheral nervous system complications.

The effects of propofol anesthesia on local cerebral glucose utilization in the rat.

The autoradiographic 14C-2-deoxy-D-glucose method was used to determine local cerebral glucose utilization (LCGU) during propofol anesthesia and recovery in 52 regions of the rat brain. Control rats intravenously received 5 ml.kg-1.h-1 of the egg-oil-glycerol emulsion that constitutes the vehicle for propofol. Anesthetized animals received an iv bolus of propofol (20 mg/kg) followed by continuous infusion of the anesthetic at 12.5, 25, or 50 mg.kg-1.h-1 for 1 h prior to injection of 14C-2-deoxy-D-glucose and for the following 45 min. In addition, a fifth group of animals were studied immediately after awakening from a 20 mg/kg bolus of propofol as indicated by the first reappearance of head lift. All rats were spontaneously breathing room air throughout the experimental procedure. The general pattern of the cerebral metabolic response to propofol anesthesia was a dose-related, widespread depression of LCGU. At the three infusion rates of propofol tested, overall mean LCGU was reduced by 33%, 49%, and 55%, respectively, and significant decreases were observed in 60%, 85%, and 90% of the regions assayed. These effects were rapidly reversible, since in the recovery group, LCGU returned to near control values in the majority of the brain areas. Although all of the anatomofunctional systems (sensorimotor, extrapyramidal, limbic, and reticular) were involved, forebrain structures showed a greater sensitivity to the depressant action of propofol than did hindbrain regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Motor tele-rehabilitation in post-stroke patients

Primary objective: The advanced communication technology may allow rehabilitative interventions to patients living at home from a remote provider. We evaluated the effects of a tele-rehabilitation system for the therapy of arm motor impairments due to a stroke. Research design: Experimental observational study. Methods and procedures: We selected five patients suffering from mild/intermediate arm motor impairments due to a long-lasting ischaemic stroke. Two workstations were utilized, one in the patients house and the other in the rehabilitation hospital, connected through the phone lines. A virtual reality based software allowed the patient to perform adequate motor tasks created by the physiotherapist. During performance, the patient could see not only their movement but also the correct trajectory that they had to accomplish. The feedback derived from the patients action, its outcome, and feedback from the supervision of the physiotherapist may favour the acquisition of new motor abilities. Main outcome measures: The arm motor performance and the activities of daily living were evaluated using the Fugl-Meyer and Functional Independence Measure scale, together with the determination of the velocity and duration of 10 representative reaching movements. Results: Subjects underwent the tele-rehabilitation programme for 4 weeks. The therapy significantly improved the Fugl-Meyer mean score, the mean duration and the velocity of the movements, but not the Functional Independence Measure scale score. Conclusions: These results indicated that this tele-rehabilitation system did not appear to adversely affect rehabilitation; rather it may improve arm motor deficits due to a stroke. If these evidences are further confirmed, tele-rehabilitation may represent a new home-based therapy to treat disabled people.